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Correspondence re: S. E. Blutt, T. C. Polek, L. V. Stewart, M. W. Kattan, and N. L. Weigel, A Calcitriol Analogue, EB1089, Inhibits the Growth of LNCaP Tumors in Nude Mice. Cancer Res., 60: 779–782, 2000.

Departments of Cancer Biology and Public Health Sciences Comprehensive Cancer Center of W ake Forest University Winston-Salem, North Carolina 27157

Bal L. Lokeshwar

Department of Urology University of Miami School of Medicine Miami, Florida 33101

Kerry L. Burnstein

Department of Molecular and Cellular Pharmacology University of Miami School of Medicine Miami, Florida 33101

Letter

We read with interest the report by Blutt et al. (1) , demonstrating inhibition of the growth of LNCaP prostate cancer cells in vivo by the calcitriol analogue, EB1089. We reported previously significant inhibitory effects of EB1089 on the proliferation of prostate cancer cells in vivo in the Dunning MAT LyLu prostate cancer model, a model of androgen-insensitive, metastatic prostate cancer. In addition, we showed that EB1089 significantly inhibits prostate cancer metastasis, the primary cause of death in men with prostate cancer, and that this effect can be achieved without inducing cachexia or unacceptable levels of hypercalcemia (2) . The report by Blutt et al. is consistent with the hypothesis that vitamin D plays an important role in the natural history of prostate cancer (3) and, with our findings that less calcemic analogues of calcitriol, such as EB1089, hold promise as therapeutic agents (4) .

Received 3/ 6/00. Accepted 3/16/01.

REFERENCES

1. Blutt S. E., Polek T. C., Stewart L. V., Kattan M. W., Weigel N. L. A calcitriol analogue, EB1089, inhibits the growth of LNCaP tumors in nude mice. Cancer Res., 60: 779-782, 2000.[Abstract/Free Full Text]
2. Lokeshwar B. L., Schwartz G. G., Selzer M. G., Burnstein K. L., Zhuang S-H., Block N. L., Binderup L. Inhibition of prostate cancer metastasis in vivo: a comparison of 1,25-dihydroxyvitamin D (calcitriol) and EB1089. Cancer Epidemiol. Biomark. Prev., 6: 241-248, 1999.
3. Schwartz G. G., Hulka B. S. Is vitamin D deficiency a risk factor for prostate cancer?. Anticancer Res., 10: 1307-1311, 1990.[Medline]
4. Schwartz G. G., Oeler T. A., Uskokovic M. R., Bahnson R. R. Human prostate cancer cells: inhibition of proliferation by vitamin D analogs. Anticancer Res., 14: 1077-1081, 1994.[Medline]

Reply

Department of Molecular and Cellular Biology Baylor College of Medicine Houston, Texas 77030

Lokeshwar et al. (1) have made the interesting finding that although the growth of MAT LyLu tumors was minimally affected by EB1089 treatment, tumor metastasis to the lung was reduced. Their finding that the MAT LyLu cells had undetectable levels of functional vitamin D receptors suggests that there may be systemic effects of EB1089 on tumor metastasis. However, the results of these experiments should be interpreted with caution because the EB1089 treatment caused a 19% elevation of serum calcium to a clinically unacceptable level (12.7 mg/dl). Nonetheless, both the Lokeshwar study (1) and our study (2) suggest that EB1089 or other less calcemic analogues are promising candidates for the treatment of prostate cancer.

REFERENCES

1. Lokeshwar B. L., Schwartz G. G., Selzer M. G., Burnstein K. L., Zhuang S-H., Block N. L., Binderup L. Inhibition of prostate cancer metastasis in vivo: a comparison of 1,25-dihydroxyvitamin D (calcitriol) and EB1089. Cancer Epidemiol. Biomark. Prev., 6: 241-248, 1999.
2. Blutt S. E., Polek T. C., Stewart L. V., Kattan M. W., Weigel N. L. A calcitriol analogue, EB1089, inhibits the growth of LNCaP tumors in nude mice. Cancer Res., 60: 779-782, 2000.

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